During partial bladder outlet obstruction (PBOO), studies in humans and in experimental animals have shown that the bladder undergoes a series of steps that enable it to compensate for the obstruction without failing to function. Eventually in many cases these steps are followed by other processes that result in the failure of compensation. During all of these processes the smooth muscle cells in the bladder are under the control of a series of signaling systems that play an important role in compensation. Not much is known about alterations in these systems. In order to improve our understanding of these processes, we have formulated the following central hypothesis: The process that occurs during partial bladder outlet obstruction that results in functional compensation is dependent on alterations in lipid-dependent second messengers such as IP3, phospholipase D products, and arachidonic acid. A secondary hypothesis is that eventual failure of compensation occurs due to still other derangements in these second messengers. As a result of these hypotheses we have proposed the following specific aims: Aim 1: to determine if the concentration of IP3 in the detrusor muscle undergoes either increases or decreases during PBOO and to determine if these changes are reversed during the reversal of PBOO. We will examine the levels of IP3 both in unstimulated muscle and in muscle stimulated by agonists such as carbachol or ATP. Aim 2: to determine if the activity of phospholipase D in detrusor muscle is either increased or decreased during PBOO and to determine if these changes are reversed during the reversal of PBOO. We will examine the activation of PLD both in unstimulated muscle and in muscle stimulated by either carbachol or ATP. Aim 3: to determine if the activity ofphospholipase A2 in detrusor muscle is either increased or decreased during PBOO and to determine if these changes are reversed during reversal of PBOO. We will examine the activation of PLA2 both in unstimulated muscle and in muscle stimulated by either carbachol or ATP. Phospholipase A2 activity will be determined by the measurement of arachidonate release from tissues prelabeled with [3H] arachidonic acid. We will also determine which isoform of PLA2 is most important in detrusor muscle by using selective inhibitors of the different PLA2 isoforms.